Interaction between HSP60 and β-catenin promotes metastasis
Interaction between HSP60 and β-catenin promotes metastasis
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DOI：
10.1093/carcin/bgp087
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发表时间：
2009-06-01
期刊：
影响因子：
4.7
通讯作者：
Wu, Kou-Juey
中科院分区：
文献类型：
--
作者：
Tsai, Ya-Ping;Yang, Muh-Hwa;Wu, Kou-Juey
热休克蛋白60（HSP 60）在帮助许多新合成的蛋白质达到其天然形式方面起着至关重要的作用。在具有转移的不同类型的人类癌症（例如胰腺癌和大肠癌）中观察到增加的HSP 60表达。然而，HSP 60在转移中的作用仍然知之甚少。β-连环蛋白的异常激活在肿瘤的发生和转移中起关键作用。在这里，我们表明，过度表达HSP 60诱导转移表型在体外和体内。HSP 60与β-连环蛋白相互作用，通过顶端结构域增加β-连环蛋白蛋白水平并增强其转录活性。短干扰RNA介导的β-连环蛋白抑制逆转了HSP 60过表达引起的转移活性HSP 60诱导β-连环蛋白不需要蛋白体活性。HSP 60和核β-catenin的共表达预示着转移性头颈癌患者的预后不良。这些结果暗示了HSP 60在转移中的新作用。
Heat shock protein 60 (HSP60) plays an essential role in assisting many newly synthesized proteins to reach their native forms. Increased HSP60 expression is observed in different types of human cancers with metastasis (e.g. pancreatic cancer and large bowel carcinoma). However, the role of HSP60 in metastasis remains little known. Aberrant activation of beta-catenin plays a key role in tumorigenesis and metastasis. Here, we show that overexpression of HSP60 induces metastatic phenotypes in vitro and in vivo. HSP60 interacts with beta-catenin, increases beta-catenin protein levels through the apical domain and enhances its transcriptional activity. Short-interference RNA-mediated repression of beta-catenin reverts metastatic activity caused by HSP60 overexpression. Proteosomal activity is not required for the induction of beta-catenin by HSP60. Coexpression of HSP60 and nuclear beta-catenin predicts a worse prognosis of metastatic head and neck cancer patients. These results implicate a novel role of HSP60 in metastasis.